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https://hdl.handle.net/2440/99218
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Type: | Journal article |
Title: | Peroxidase enzymes regulate collagen biosynthesis and matrix mineralization by cultured human osteoblasts |
Author: | DeNichilo, M. Shoubridge, A. Panagopoulos, V. Liapis, V. Zysk, A. Zinonos, I. Hay, S. Atkins, G. Findlay, D. Evdokiou, A. |
Citation: | Calcified Tissue International, 2016; 98(3):294-305 |
Publisher: | Springer |
Issue Date: | 2016 |
ISSN: | 0171-967X 1432-0827 |
Statement of Responsibility: | Mark O. DeNichilo, Alexandra J. Shoubridge, Vasilios Panagopoulos, Vasilios Liapis, Aneta Zysk, Irene Zinonos, Shelley Hay, Gerald J. Atkins, David M. Findlay, Andreas Evdokiou |
Abstract: | The early recruitment of inflammatory cells to sites of bone fracture and trauma is a critical determinant in successful fracture healing. Released by infiltrating inflammatory cells, myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, whose functional involvement in bone repair has mainly been studied in the context of providing a mechanism for oxidative defense against invading microorganisms. We report here novel findings that show peroxidase enzymes have the capacity to stimulate osteoblastic cells to secrete collagen I protein and generate a mineralized extracellular matrix in vitro. Mechanistic studies conducted using cultured osteoblasts show that peroxidase enzymes stimulate collagen biosynthesis at a post-translational level in a prolyl hydroxylase-dependent manner, which does not require ascorbic acid. Our studies demonstrate that osteoblasts rapidly bind and internalize both MPO and EPO, and the catalytic activity of these peroxidase enzymes is essential to support collagen I biosynthesis and subsequent release of collagen by osteoblasts. We show that EPO is capable of regulating osteogenic gene expression and matrix mineralization in culture, suggesting that peroxidase enzymes may play an important role not only in normal bone repair, but also in the progression of pathological states where infiltrating inflammatory cells are known to deposit peroxidases. |
Keywords: | Peroxidase enzymes Osteoblasts Collagen biosynthesis Matrix mineralization |
Rights: | © Springer Science+Business Media New York 2015 |
DOI: | 10.1007/s00223-015-0090-6 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/627015 http://purl.org/au-research/grants/nhmrc/1050694 |
Published version: | http://dx.doi.org/10.1007/s00223-015-0090-6 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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